NCT04311502

Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study

A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 104 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to compare a 3-month rifapentine (RPT)/clofazimine (CFZ)-containing regimen with a CFZ loading dose with the 6-month standard of care (SOC) regimen for drug-susceptible (DS) tuberculosis (TB).

Detailed description

This study compared a 3-month rifapentine (RPT)/clofazimine (CFZ)-containing regimen with a CFZ loading dose with the 6-month standard of care (SOC) for drug-susceptible (DS) tuberculosis (TB). Randomization was stratified based on HIV status and the presence of advanced disease as determined by chest X-ray. Participants were randomized to one of three arms: * Arm 1 (Experimental): rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + CFZ 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks * Arm 2 (SOC): rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks * Arm C (PK-only subgroup): PHZE + CFZ 100 mg once daily for 4 weeks; then remain on study, off study medications and treated according to SOC (RHZE for 4 weeks; then RH for 18 weeks) All participants received pyridoxine (vitamin B6) with each dose of isoniazid (INH) based on current local, national or international dosing guidelines. Arm 1 participants were treated for 13 weeks (including a 2-week CFZ loading dose of 300 mg daily). Arm 2 participants were treated for 26 weeks, and Arm C participants were treated for 4 weeks. All participants in Arms 1, 2, and C were followed from randomization to Week 65. On June 1, 2023, the Data and Safety Monitoring Board (DSMB) recommended that the study permanently close to accrual because of the high rate of treatment failure and TB recurrence. The A5362 team, NIAID and DAIDS leadership, and ACTG leadership concurred with the DSMB's recommendation and the study was closed to accrual on June 2, 2023. A letter of amendment was created that extended follow-up to 117 weeks for some participants in Arm 1. Due to the early close to accrual, a primary analysis report forming the basis of the primary trial manuscript used data collected at study visits up to and including the date when the last enrolled participant completed the week 26 study visit (September 25. 2023). Another final analysis was performed using data collected at study visits up to the date when the last enrolled participant completed the week 65 assessment. Study visits included physical examinations; blood, urine, and/or sputum collection; chest X-rays; and electrocardiograms (ECG).

Conditions

• HIV
• Tuberculosis

Interventions

Type	Name	Description
DRUG	Rifapentine	1200 mg once daily
DRUG	Rifampicin	600 mg once daily
DRUG	Isoniazid	300 mg once daily
DRUG	Pyrazinamide	1000mg once daily if weight is 40 to \<55kg; 1500mg once daily if weight is 55 to \<71kg; 2000mg once if weight is ≥71kg
DRUG	Ethambutol	800 mg once daily if weight is 40 to \<55kg; 1200 mg once daily if weight is 55 to \<71kg; 1600mg once if weight is ≥71kg
DRUG	Clofazimine loading dose	300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
DRUG	Clofazimine 100 MG	100 mg once daily

Timeline

• Start date: 2021-11-05
• Primary completion: 2024-06-24
• Completion: 2025-06-24
• First posted: 2020-03-17
• Last updated: 2025-08-27
• Results posted: 2025-08-27

Locations

6 sites across 5 countries: Haiti, India, Malawi, South Africa, Zimbabwe

Regulatory

• FDA-regulated drug study